Abstract：
BACKGROUND: Several animal models have been established to investigate the mechanisms of obliterative bronchiolitis after lung transplantation. In this study, we compared three prevalent murine models of obliterative bronchiolitis in terms of several basic pathologic changes in a relatively short span of time after transplantation.
METHODS: Each of the recipient mice simultaneously received orthotopic, intra-omental and subcutaneous tracheal transplantation in both syngeneic and allogeneic settings. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day 14, 21 and 28 after transplantation for histological and immunohistochemical analyses.
RESULTS: Syngeneic tracheal grafts from different transplant sites retained normal histologic structures, while their corresponding allografts demonstrated more occlusion of the airway lumen as well as more infiltration of CD4(+)/CD8(+) mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with two heterotopic allografts, orthotopic allografts had less occlusion of the tracheal lumen as well as less infiltration of CD4(+)/CD8(+) mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized vessels (P<0.05).
CONCLUSIONS: Orthotopic tracheal transplantation in mice can be considered as a model to study early stages of obliterative bronchiolitis, and heterotopic tracheal transplantation can be a model for late stages of obliterative bronchiolitis.
METHODS: Each of the recipient mice simultaneously received orthotopic, intra-omental and subcutaneous tracheal transplantation in both syngeneic and allogeneic settings. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day 14, 21 and 28 after transplantation for histological and immunohistochemical analyses.
RESULTS: Syngeneic tracheal grafts from different transplant sites retained normal histologic structures, while their corresponding allografts demonstrated more occlusion of the airway lumen as well as more infiltration of CD4(+)/CD8(+) mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with two heterotopic allografts, orthotopic allografts had less occlusion of the tracheal lumen as well as less infiltration of CD4(+)/CD8(+) mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized vessels (P<0.05).
CONCLUSIONS: Orthotopic tracheal transplantation in mice can be considered as a model to study early stages of obliterative bronchiolitis, and heterotopic tracheal transplantation can be a model for late stages of obliterative bronchiolitis.
摘要：
背景：已经建立了几种动物模型来研究肺移植后闭塞性细支气管炎的机制。在这项研究中,我们比较了三种流行的小鼠闭塞性细支气管炎模型在移植后较短时间内的几种基本病理变化。
方法：每个受体小鼠同时接受原位，同种异体和同种异体的大网膜内和皮下气管移植。未给予免疫抑制治疗。在移植后第14、21和28天收获气管移植物用于组织学和免疫组织化学分析。
结果：来自不同移植部位的同种异体气管移植物保留了正常的组织学结构，而相应的同种异体移植物表现出更多的气道管腔闭塞以及更多的CD4（+）/CD8（+）单核细胞和肌成纤维细胞的浸润，但在指定时间再生上皮和新生血管较少（P<0.05）。与两种异位同种异体移植物相比，原位同种异体移植物气管腔闭塞较少，CD4(+)/CD8(+)单核细胞和肌成纤维细胞浸润较少，但更多的再生上皮和新生血管化血管（P<0.05）。
结论：小鼠原位气管移植可作为早期闭塞性细支气管炎的研究模型。异位气管移植可以作为晚期闭塞性细支气管炎的模型。
方法：每个受体小鼠同时接受原位，同种异体和同种异体的大网膜内和皮下气管移植。未给予免疫抑制治疗。在移植后第14、21和28天收获气管移植物用于组织学和免疫组织化学分析。
结果：来自不同移植部位的同种异体气管移植物保留了正常的组织学结构，而相应的同种异体移植物表现出更多的气道管腔闭塞以及更多的CD4（+）/CD8（+）单核细胞和肌成纤维细胞的浸润，但在指定时间再生上皮和新生血管较少（P<0.05）。与两种异位同种异体移植物相比，原位同种异体移植物气管腔闭塞较少，CD4(+)/CD8(+)单核细胞和肌成纤维细胞浸润较少，但更多的再生上皮和新生血管化血管（P<0.05）。
结论：小鼠原位气管移植可作为早期闭塞性细支气管炎的研究模型。异位气管移植可以作为晚期闭塞性细支气管炎的模型。
